Image_1_Long-term trajectories of BMI and cumulative incident metabolic syndrome: A cohort study.png

BackgroundBody mass index (BMI) has been widely recognized as a risk factor for metabolic syndrome (MetS). However, the relationship between the trajectory of BMI and cumulative incident MetS is still unclear. We investigate the associations of long-term measurements of BMI with MetS among young adults in the China Health and Nutrition Survey.MethodsWe enrolled individuals aged 10 to 20 at baseline with recorded BMI at each follow-up interview, and 554 participants were finally included in our study. The assessment and incidence of MetS were evaluated by blood tests and physical examinations in their adulthood. A latent class growth mixed model was used to identify three BMI trajectory patterns: a low baseline BMI with slow development (low-slow, n=438), a low baseline BMI with fast development (low-fast, n=66), and a high baseline BMI with fast development (high-fast, n=50). Logistic regression was used to explore the relationship between different BMI trajectories and the incidence of MetS.ResultDuring a follow-up of 16 years, 61 (11.01%) participants developed MetS. The combination of elevated triglycerides and reduced high-density lipoprotein cholesterol was most frequent in diagnosed MetS. In multivariate adjusted models, the low-fast and high-fast BMI trajectories showed a significantly higher risk of MetS than those with the low-slow BMI trajectory (low-high: OR = 3.40, 95% CI: 1.14-10.13, P ConclusionOur study identified three BMI trajectories in young adults and found that long-term measurements of BMI were also associated with cumulative incident MetS.</p

Table_1_Long-term trajectories of BMI and cumulative incident metabolic syndrome: A cohort study.docx

BackgroundBody mass index (BMI) has been widely recognized as a risk factor for metabolic syndrome (MetS). However, the relationship between the trajectory of BMI and cumulative incident MetS is still unclear. We investigate the associations of long-term measurements of BMI with MetS among young adults in the China Health and Nutrition Survey.MethodsWe enrolled individuals aged 10 to 20 at baseline with recorded BMI at each follow-up interview, and 554 participants were finally included in our study. The assessment and incidence of MetS were evaluated by blood tests and physical examinations in their adulthood. A latent class growth mixed model was used to identify three BMI trajectory patterns: a low baseline BMI with slow development (low-slow, n=438), a low baseline BMI with fast development (low-fast, n=66), and a high baseline BMI with fast development (high-fast, n=50). Logistic regression was used to explore the relationship between different BMI trajectories and the incidence of MetS.ResultDuring a follow-up of 16 years, 61 (11.01%) participants developed MetS. The combination of elevated triglycerides and reduced high-density lipoprotein cholesterol was most frequent in diagnosed MetS. In multivariate adjusted models, the low-fast and high-fast BMI trajectories showed a significantly higher risk of MetS than those with the low-slow BMI trajectory (low-high: OR = 3.40, 95% CI: 1.14-10.13, P ConclusionOur study identified three BMI trajectories in young adults and found that long-term measurements of BMI were also associated with cumulative incident MetS.</p

Image_2_Long-term trajectories of BMI and cumulative incident metabolic syndrome: A cohort study.png

BackgroundBody mass index (BMI) has been widely recognized as a risk factor for metabolic syndrome (MetS). However, the relationship between the trajectory of BMI and cumulative incident MetS is still unclear. We investigate the associations of long-term measurements of BMI with MetS among young adults in the China Health and Nutrition Survey.MethodsWe enrolled individuals aged 10 to 20 at baseline with recorded BMI at each follow-up interview, and 554 participants were finally included in our study. The assessment and incidence of MetS were evaluated by blood tests and physical examinations in their adulthood. A latent class growth mixed model was used to identify three BMI trajectory patterns: a low baseline BMI with slow development (low-slow, n=438), a low baseline BMI with fast development (low-fast, n=66), and a high baseline BMI with fast development (high-fast, n=50). Logistic regression was used to explore the relationship between different BMI trajectories and the incidence of MetS.ResultDuring a follow-up of 16 years, 61 (11.01%) participants developed MetS. The combination of elevated triglycerides and reduced high-density lipoprotein cholesterol was most frequent in diagnosed MetS. In multivariate adjusted models, the low-fast and high-fast BMI trajectories showed a significantly higher risk of MetS than those with the low-slow BMI trajectory (low-high: OR = 3.40, 95% CI: 1.14-10.13, P ConclusionOur study identified three BMI trajectories in young adults and found that long-term measurements of BMI were also associated with cumulative incident MetS.</p

Enzyme-Assisted Metabolically Coated Bimetallic Thalassiosira pseudonana Nanosilica as a Surface-Enhanced Raman Scattering Substrate for Specific Screening of Prostate Cancer Individuals

Multicomponent heteronanostructures offering catalytic and optical properties have applications across various fields. Photonic crystals (diatom frustules) coated with Au and copper chalcogenide domains represent a unique nanosystem that integrates multiple plasmon resonances from guided-mode resonance, conduction electrons, and valence holes in a single nanoscale system. In this work, we fabricate an enzyme-assisted photonic crystal-enhanced plasmonic nanosystem using a live diatom (Thalassiosira pseudonana) for surface-enhanced Raman scattering (SERS) quantification of sarcosine, an early stage prostate cancer (PCa) biomarker. The biosynthesized heteronanostructure was constructed by coating bimetallic nanoparticles (Au/CuX) on the diatom frustule via a two-stage cultivation process. A silaffin peptide-tagged sarcosine oxidase (SoX) was designed for specific substrate recognition and oriented conjunction. The components were coupled into a single entity (SoX-immobilized Au/CuX-coated frustule, BioNPS) to overcome the interenzyme distance and analyte trade-offs between mass transport. The sarcosine detection by BioNPS outperforms suspended bimetallic nanoparticles and single NP-coated diatom frustules. The improvement is attributed to the coupling of photonic frustule guided-mode resonance to the localized surface plasmonic resonance of bimetallic NPs via both electromagnetic and CT mechanisms. The cascade reaction in close proximity greatly enhances the catalytic efficiency by 5.47-fold compared to the solution-phase assay. The biochem nanosystem precisely detects tiny sarcosine concentration changes in the urine samples of PCa patients and healthy individuals. As a proof of concept, the in vivo fabrication of photonic/plasmonic heterostructures with tunable properties holds great promise for noninvasive biomarker screening

Stabilization of Human Tyrosine Hydroxylase in Maltodextrin Nanoparticles for Delivery to Neuronal Cells and Tissue

Enzyme replacement therapy (ERT) is a therapeutic approach envisioned decades ago for the correction of genetic disorders, but ERT has been less successful for the correction of disorders with neurological manifestations. In this work, we have tested the functionality of nanoparticles (NP) composed of maltodextrin with a lipid core to bind and stabilize tyrosine hydroxylase (TH). This is a complex and unstable brain enzyme that catalyzes the rate-limiting step in the synthesis of dopamine and other catecholamine neurotransmitters. We have characterized these TH-loaded NPs to evaluate their potential for ERT in diseases associated with TH dysfunction. Our results show that TH can be loaded into the lipid core maltodextrin NPs with high efficiency, and both stability and activity are maintained through loading and are preserved during storage. Binding to NPs also favored the uptake of TH to neuronal cells, both in cell culture and in the brain. The internalized NP-bound TH was active as we measured an increase in intracellular L-Dopa synthesis following NP uptake. Our approach seems promising for the use of catalytically active NPs in ERT to treat neurodegenerative and neuropsychiatric disorders characterized by dopamine deficiency, notably Parkinson’s disease

Representation of electrostatic surface potentials.

<p>The electrostatic potentials are calculated on the X-ray structures of 14-3-3γ (PDB 2B05) (A, C, E) and 14-3-3ζ (PDB 2O02) (B, D, F). The electrostatic potentials are visualized on the solvent accessible surface in panel A–D with values colored from blue to red (from +2 kT/e to −2 kT/e). Panels E and F show the iso-contours of the electrostatic potential (+1 kT/e to −1 kT/e). The area with stronger positive electrostatic potential in 14-3-3γ (A) compared with 14-3-3ζ (B) corresponds to residues in helices A, B and D in the dimerization region that involves the N-terminal from each subunit (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049671#pone.0049671.s001" target="_blank">Figure S1</a>). Positive areas are predicted to contact the membrane in an initial phase driven by the electrostatics, while the negative areas on the convex side of the protein are possibly involved in tuning the orientation of the positive dimerization region towards the membrane. The bound phosphopeptides were omitted prior to the calculations of the electrostatic potentials.</p

pH dependency of the electrostatic potential at the convex lateral side.

<p>The electrostatic potential is shown at pH values 7.0, 6.5, and 6.0 (column wise), for 14-3-3γ (A), 14-3-3ζ (B), and H158F/H195S-14-3-3γ (C).</p

MD simulations of phosphopeptide-bound (holo-14-3-3γ) and ligand-free (apo-14-3-3) structures.

<p>A) Structural deviation from the initial X-ray structure (PDB 2B05) along the simulation time (100 ns) for phosphopeptide (RAIpSLP)-free apo (green and red lines, one line for each monomer A and B) and phosphopeptide-bound holo (blue and black lines for each monomer); RMSD, root mean square deviation. B) Positional fluctuations (root mean square fluctuations (RMSF)) along the holo (black bars) and apo (blue lines) 14-3-3γ. Helices are indicated schematically as black stripes. C) Backbone ribbon overlay representation of the dimeric structures obtained at the end of the MD simulations (100 ns) of holo (blue) and apo (green) 14-3-3γ. The inset (D) shows the residues mutated in this study (Tyr117, His158, His164 and His195) in stick representation, and the averaged distance between His158 and His195 at the end of the simulations. E, F) Representation of surface electrostatic potentials, calculated on the solvent accessible surface of the MD simulated structures of holo (E) and apo (F) 14-3-3γ, colored from blue to red (from +2 kT/e to −2 kT/e).</p

Effect of phosphopeptide ligand and kosmotropic salts on the binding of 14-3-3γ to negatively charged membranes.

<p>A) Representative sensorgrams for the binding of 14-3-3γ as purified (10 µM subunit) prepared in HBS-N buffer (10 mM Na-Hepes, pH 7.4, 150 mM NaCl) to liposomes made of PC∶PBPS (⋅⋅⋅⋅⋅⋅⋅⋅), or PC (– – –), and for the binding of 14-3-3γ (10 µM subunit) with THp-(1-43) (20 µM) in HBS-N buffer to liposomes made of PC∶PBPS (–⋅⋅–⋅⋅–) or PC (^_______). B) The dependence of SPR responses (difference of RUs for binding to liposomes of PC∶PBPS and PC) on the subunit concentration of 14-3-3γ, alone (•) or with 2-fold concentration of THp-(1-43) (○). The binding isotherms were fitted using a single-rectangle, two-parameter equation providing S_0.5 values of 2.0±0.2 µM for the protein alone and 1.2±0.2 µM for the protein-phosphopeptide complex. C) Sensorgram for the binding to liposomes of PC∶PBPS of d14-3-3γ (extensively dialyzed in 10 mM Na-Hepes, pH 7.4) and further diluted in HBS-N buffer, alone (^_______) or with a 2-fold concentration of THp-(1-43) (–⋅⋅–⋅⋅–) (running buffer HBS-N in both cases), and with 50 mM Na-phosphate, pH 7.4 (running buffer HBS-N with 50 mM Na-phosphate) (⋅⋅⋅⋅⋅⋅⋅⋅) or 50 mM Na-sulphate, pH 7.4 (running buffer HBS-N with 50 mM Na-sulphate) (– – –).</p

Effect of mutation of specific histidine residues and of pH on the binding of 14-3-3γ to liposomes of PC∶PBPS (1∶1) measured by surface plasmon resonance (SPR).

<p>A) Representative sensorgrams for the binding of H158F- (⋅⋅⋅⋅⋅⋅⋅⋅), H195S- (–⋅⋅–⋅⋅–) and H158F/H195S- (– – –), comparative to wt-14-3-3γ (^_______). The sensorgrams for H164E- and Y117F-14-3-3γ were similar to that of wt-14-3-3γ. The protein samples were prepared in 100 mM Na-phosphate, pH 7.4. B) Representative sensorgrams for the binding of wt-14-3-3γ as isolated, and diluted in either 100 mM Na-phosphate, pH 6.0 (^_______), 100 mM Na-phosphate, pH 7.0 (⋅⋅⋅⋅⋅⋅⋅⋅), or 100 mM Tris-HCl, pH 8.0 (– – –). For both (A) and (B), liposomes were immobilized on the sensor chip at 4000–6000 RU, and each protein was applied at ∼50 µM subunit and injected at 25°C. The sample preparation buffers were used as running buffer.</p